We propose a definitive studtt to elucidate the three-dimensional structure of Pseudomonas aeruginosa exotoxin A by x-ray crystallographic methods. The toxin, which is implicated as a major determinant of lethality in P. aeruginosa infections, has been studied intensively in recent years (i) with regard to its role in, and immunization against, infection by P. aeruginosa, (ii) as a system for understanding the actions of toxic proteins, and (iii) as a potential effector moiety for constructing targeted cytotoxic agents. We have recently found conditions for growing highly ordered crystals of exotoxin A and for obtaining heavy atom derivatives necessary for structure determination, and we have solved the structure to 5.5 A resolution. The quality of the low resolution data indicate that determination of the three-dimensional structure of the molecule at high resolution is imminently feasible. The structure will provide an important framework for future applied and basic research on this and related toxins. Our projections are that exotoxin A may be the first major bacterial toxin whose structure is described at three-dimensional level.